Two major forces in clinical medicine on the horizon are expected to change the paradigm of clinical care. One is personalized genomic medicine (PGM), which seeks to harness knowledge about the genetic endowment of the individual to individually tailor specific medical therapies. The second driving force in healthcare today is to conduct comparative effectiveness research (CER) to directly compare the effectiveness, and sometimes the cost, of alternative therapies or diagnostic modalities for the same disease or condition. As CER is conducted on alternative approaches to PGM, it is important for it to appropriately address the ethical, legal, and social concerns raised by genomic research, which have been elucidated by the ELSI program. To date, however, there has been no significant attempt to determine how the design and conduct of CER research on PGM should be shaped by the lessons from the ELSI program. This project aims to respond to this gap by comprehensively examining the specific ethical, legal, and social issues raised by comparative effectiveness research on personalized genomic medicine (CER/PGM), and to propose a set of points to consider in designing and conducting this research so that it can be carried out in an ethical, legal, and socially appropriate manner. PUBLIC HEALTH RELEVANCE: Both personalized genomic medicine and comparative effectiveness research are becoming increasingly important tools for improving the quality of health care and controlling health care costs, and the number of studies comparing the effectiveness of various personalized genomic interventions and approaches is expected to grow. While there has been a considerable effort to understand and address the ethical, legal, and social implications of personalized genomic medicine, there has been little attempt to apply this knowledge to the design, conduct, and translation of comparative effectiveness research on personalized genomic medicine. This project will identify these concerns and suggest how they can be appropriately addressed by this type of research.